Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B

Anna S F Lok, Ching Lung Lai, Nancy Leung, Guang Bi Yao, Zhen Yu Cui, Eugene R Schiff, Jules L. Dienstag, E. Jenny Heathcote, Nancy R. Little, Dorothea A. Griffiths, Stephen D. Gardner, Mary Castiglia

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Abstract

Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of the lamivudine-treated patients in year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine resistance resistant stable during the first 4 years with mutations and increased afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.

Original languageEnglish
Pages (from-to)1714-1722
Number of pages9
JournalGastroenterology
Volume125
Issue number6
DOIs
StatePublished - Dec 1 2003

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Lamivudine
Chronic Hepatitis B
Safety
Liver Diseases
Mutation
Hepatitis
Therapeutics
Hepatitis B e Antigens
Liver

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Lok, A. S. F., Lai, C. L., Leung, N., Yao, G. B., Cui, Z. Y., Schiff, E. R., ... Castiglia, M. (2003). Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B. Gastroenterology, 125(6), 1714-1722. https://doi.org/10.1053/j.gastro.2003.09.033

Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B. / Lok, Anna S F; Lai, Ching Lung; Leung, Nancy; Yao, Guang Bi; Cui, Zhen Yu; Schiff, Eugene R; Dienstag, Jules L.; Heathcote, E. Jenny; Little, Nancy R.; Griffiths, Dorothea A.; Gardner, Stephen D.; Castiglia, Mary.

In: Gastroenterology, Vol. 125, No. 6, 01.12.2003, p. 1714-1722.

Research output: Contribution to journalArticle

Lok, ASF, Lai, CL, Leung, N, Yao, GB, Cui, ZY, Schiff, ER, Dienstag, JL, Heathcote, EJ, Little, NR, Griffiths, DA, Gardner, SD & Castiglia, M 2003, 'Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B', Gastroenterology, vol. 125, no. 6, pp. 1714-1722. https://doi.org/10.1053/j.gastro.2003.09.033
Lok, Anna S F ; Lai, Ching Lung ; Leung, Nancy ; Yao, Guang Bi ; Cui, Zhen Yu ; Schiff, Eugene R ; Dienstag, Jules L. ; Heathcote, E. Jenny ; Little, Nancy R. ; Griffiths, Dorothea A. ; Gardner, Stephen D. ; Castiglia, Mary. / Long-Term Safety of Lamivudine Treatment in Patients with Chronic Hepatitis B. In: Gastroenterology. 2003 ; Vol. 125, No. 6. pp. 1714-1722.
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abstract = "Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10{\%} of the lamivudine-treated patients in year 1 and in 18{\%}-21{\%} in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43{\%} in year 1 to >80{\%} in year 3. Ten hepatic decompensation events occurred in 8 (<1{\%}) lamivudine-treated patients. Fifty-three (5{\%}) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23{\%} in year 1 to 65{\%} in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0{\%}-2{\%}) and LDR SAEs (1{\%}-10{\%}) among patients with lamivudine resistance resistant stable during the first 4 years with mutations and increased afterward to 6{\%} (P = 0.03) and 20{\%} (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.",
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AU - Lok, Anna S F

AU - Lai, Ching Lung

AU - Leung, Nancy

AU - Yao, Guang Bi

AU - Cui, Zhen Yu

AU - Schiff, Eugene R

AU - Dienstag, Jules L.

AU - Heathcote, E. Jenny

AU - Little, Nancy R.

AU - Griffiths, Dorothea A.

AU - Gardner, Stephen D.

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N2 - Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of the lamivudine-treated patients in year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine resistance resistant stable during the first 4 years with mutations and increased afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.

AB - Background & Aims: Data on the long-term safety of lamivudine are limited. The aim of this analysis was to determine the incidence of hepatitis flares, hepatic decompensation, and liver-disease-related (LDR) serious adverse events (SAE) during long-term lamivudine treatment. Methods: We reviewed data on 998 patients with HBeAg-positive compensated chronic hepatitis B who received lamivudine for up to 6 years (median, 4 years) and 200 patients who received placebo for 1 year. Results: Hepatitis flares occurred in 10% of the lamivudine-treated patients in year 1 and in 18%-21% in years 2-5. A temporal association between hepatitis flares and lamivudine-resistant mutations increased from 43% in year 1 to >80% in year 3. Ten hepatic decompensation events occurred in 8 (<1%) lamivudine-treated patients. Fifty-three (5%) lamivudine-treated patients experienced a total of 60 LDR SAEs. Four patients died, 2 from liver-related causes. The proportion of patients with a documented lamivudine-resistant mutation increased from 23% in year 1 to 65% in year 5. During each year of the study, patients with lamivudine-resistant mutations experienced significantly more hepatitis flares than patients without lamivudine-resistant mutations (P < 0.005). The occurrence of hepatic decompensation (0%-2%) and LDR SAEs (1%-10%) among patients with lamivudine resistance resistant stable during the first 4 years with mutations and increased afterward to 6% (P = 0.03) and 20% (P = 0.009), respectively. Conclusions: This study demonstrated that lamivudine treatment for up to 6 years has an excellent safety profile in patients with HBeAg-positive compensated liver disease, but patients with long-standing lamivudine-resistant mutations may experience worsening liver disease.

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